Perioperative treatment for resectable gastric cancer differs between Western and Asian countries. In Western countries the perioperative chemotherapy is preferred based on the results of the [inaudible] trial, however, that is not the standard of care in Asian countries. In Asian countries the adjuvant chemotherapy after D2 or more extended gastrectomy in patients with pathological phase III gastric or GE junction cancer is regarded as the standard treatment.
Nivolumab demonstrates significant efficacy in the advanced or recurrent gastric or GE junction cancer so it is expected that the efficacy of nivolumab may be obtained even in the adjuvant treatment for the pathological stage III gastric cancer.
The ATTRACTION-5 trial was a placebo-controlled, double-blinded phase III trial conducted in Asian countries, in Japan, Korea, Taiwan and China, in order to see the efficacy and safety of nivolumab plus chemotherapy to placebo plus chemotherapy in patients with pathological stage III gastric or GE junction cancer after D2 or more extended surgery. The primary endpoint was centrally assessed relapse free survival and secondary endpoints were investigator assessed relapse free survival, overall survival and safety. The trial sample size was determined at 700, assuming a hazard ratio of 0.67. The assumed hazard ratio corresponded to a three-year relapse free survival rate of 71% for the nivolumab arm and 60% for the placebo arm.
The results were a bit disappointing. We failed to demonstrate a statistically significant improvement in the relapse free survival. The hazard ratio of the nivolumab arm to the placebo arm was 0.90; that is not statistically significant. However, in the subgroup analysis the efficacy of nivolumab can be obtained in patients with PS1 and pathological stage IIIc and tumour PD-L1 expression positive. These patients would be a good candidate for future trials.